Dimethylformamide → ethyl (4S)-6-cyano-2-ethyl-8-methoxy-4-methyl-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a mixture of ethyl (4S)-6-bromo-2-ethyl-8-methoxy-4-methyl-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-carboxylate (4.1 g, 11.41 mmol; Example 62, step 7), zinc dust (0.15 g, 2.28 mmol), zinc cyanide (1.11 g, 9.47 mmol), triphenylphosphine (0.46 g, 1.77 mmol), and tris(dibenzylideneacetone)dipalladium (0) (1.57 g, 1.71 mmol) in anhydrous DMF (10 mL) was purged with argon gas for 15 minutes. The mixture was heated in a sealed tube in an oil bath at 140° C. overnight. The reaction mixture was filtered through a pad of Celite, and the filtrate concentrated under vacuum. The residue was partitioned between chloroform and aqueous EDTA monosodium salt. The mixture was stirred at room temperature for 30 minutes. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluted with 0 to 40% ethyl acetate in chloroform gradient. Collection and concentration of appropriate fractions provided the title nitrile.

Provenance & Evidence